Metformin Hydrochloride in Preventing Oral Cancer in Patients With an Oral Premalignant Lesion

This phase IIa trial studies how well metformin hydrochloride works in preventing oral cancer in patients with an oral premalignant lesion (oral leukoplakia or erythroplakia). Oral premalignant lesions look like red or whitish plaques or lesions in the mouth that do not rub off and can be associated with a higher risk of cancer. Metformin hydrochloride may help prevent oral cancer from forming in patients with an oral premalignant lesion.

Inclusion Criteria: * Participants with oral leukoplakia or erythroplakia with mild, moderate, or severe histologic dysplasia, or hyperplasia not associated with mechanical factors such as ill-fitted dentures * Measurable disease - minimum lesion size of 8 x 3 mm before initial biopsy * Karnofsky performance status \>= 70% * Leukocytes \>= 3,000/microliter * Absolute neutrophil count \>= 1,000/microliter * Platelets \>= 100,000/microliter * Total bilirubin =\< 1.5 × institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\ 40 mL/min using the Cockcroft-Gault equation * Life expectancy \> 3 months * Willing to use adequate contraception (barrier method, abstinence, subject has had a vasectomy or partner is using effective birth control or is postmenopausal) for the duration of study participation * Ability to take oral medication * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Patients with diabetes who are taking insulin or oral agents * History of diabetic ketoacidosis * Participants may not be receiving any other investigational agents within past 3 months * History of allergic reactions attributed to compounds of similar chemical composition to metformin or prior use of metformin within the last year * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, human immunodeficiency virus (HIV)-positive, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Oral carcinoma in situ * History of chronic alcohol use or abuse defined as any one of the following: a) average consumption of 3 or more alcohol containing beverages daily in the past 12 months; b) consumption of 7 or more alcoholic beverages within a 24 hour (hr) period in the past 12 months * Glycated hemoglobin (HbA1c) \> 8% * Pregnancy or nursing women * Acute or chronic liver disease, evidence of hepatitis (infectious or autoimmune), cirrhosis or portal hypertension * History of renal disease * History of prior head and neck squamous cell carcinoma (HNSCC) unless curatively treated for \>= 1 year * Have received chemotherapy and/or radiation for any malignancy (excluding non-melanoma skin cancer and cancers confined to organs with removal as only treatment) in the past 2 years; ongoing adjuvant hormonal therapy for breast cancer is allowed